Effectiveness and Safety of Apixaban Initiation Following Newly-Diagnosed Atrial Fibrillation in Patients With Kidney Failure on Hemodialysis

Abstract

Rationale & Objective

Atrial fibrillation (AF) is common among patients with kidney failure treated with hemodialysis. We studied the outcomes of apixaban initiation compared with no initiation of any oral anticoagulation among patients with hemodialysis-treated kidney failure and newly diagnosed AF.

Study Design

Retrospective cohort study.

Setting & Participants

Medicare-insured patients with hemodialysis-treated kidney failure with newly diagnosed AF and without recent oral anticoagulant (OAC) use (2014-2019).

Exposure

Initiation of apixaban treatment versus no OAC initiation within 30 days of an AF diagnosis.

Outcomes

Thromboembolic and bleeding events and death within 365 days of follow-up.

Analytical Approach

Propensity-matched comparison of new apixaban users and OAC nonusers implemented using Cox proportional hazards models while accounting for competing risks.

Results

Within 30 days of the new diagnosis of AF among 63,300 previously OAC-naïve patients, 4,010 initiated apixaban and 59,290 did not initiate any OAC. After propensity matching, 3,985 apixaban users were well matched to 3,985 OAC nonusers on all measured characteristics. Median CHA₂DS₂-VASc, a multidimensional stroke risk score, was 4 (interquartile range [IQR], 3-5). Apixaban was initiated a median of 5 (IQR, 2-12) days after AF and used for a median of 59 (IQR, 37-135) days. In intention-to-treat analyses, rates of ischemic stroke were 25% lower (HR, 0.75; 95% CI, 0.57–0.97) and those of a composite outcome of thromboembolic events and cardiovascular death were 24% lower (HR, 0.76; 95% CI, 0.70-0.83) among apixaban users. Conversely, apixaban users had a 55% higher rate of hemorrhagic stroke (HR, 1.55; 95% CI, 1.03-2.33) and a 29% increased rate of clinically important bleeding (HR, 1.29; 95% CI, 1.14-1.45). The HR for all-cause mortality was 0.61 (95% CI, 0.56-0.67). Results from as-treated analyses were qualitatively consistent with intent-to-treat analyses but generally larger in magnitude.

Limitations

Potential for residual confounding from unobserved characteristics or informative censoring unaccounted for by competing risk models.

Conclusions

Among patients with hemodialysis-treated kidney failure, compared with no anticoagulation, initiation of apixaban soon after newly diagnosed AF was associated with lower risks of ischemic stroke, a composite thromboembolic end point, and all-cause mortality but higher rates of clinically meaningful bleeding.

Plain-Language Summary

In this study of existing data of patients with kidney failure receiving dialysis who were newly diagnosed with atrial fibrillation, the most common heart rhythm disorder, we found that initiating a newer blood thinner, apixaban, was associated with fewer strokes, other clotting-related cardiovascular events, and deaths compared with what was observed in patients who did not initiate any blood-thinner treatment after their atrial fibrillation diagnosis. However, patients initiating apixaban did have higher rates of bleeding events that required hospitalization or, rarely, led to death. The information presented in this study can be used to inform shared decision-making between patients and their physicians.